Establish the PK of Belinostat in Patients With Wild-type, Heterozygous, and Homozygous UGT1A1*28 Genotypes

Acrotech Biopharma

Status and phase: Completed; Phase 1

Conditions: Hematological Malignancies; Solid Tumors

Treatments: Drug: Belinostat IV

Study type: Interventional

Funder types: Industry

Identifiers

NCT02680795

SPI-BEL-106

Details and patient eligibility

About

This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype

Full description

This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype

Enrollment into all cohorts will occur simultaneously rather than sequentially. Belinostat will be administered via a 30-minute infusion once daily from Day 1 to Day 5 of one 21-day cycle. Clinical safety will be monitored in each patient. Blood samples for PK analysis will be collected from Day 1 to Day 3, and urine samples for PK analysis will be collected from Day 1 to Day 4.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient is diagnosed with advanced solid tumors or advanced hematological malignancy that is relapsed/refractory, for which no standard salvage therapy exists.
2. Patient must have received at least 1 prior systemic therapy for the current malignancy and has recovered from any toxicity of the prior therapy at screening.
3. Patient has adequate hematological and hepatic functions.

Exclusion criteria

1. Patient is taking UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) at screening.
2. Patient has HBV or HCV
3. Patient has a known HIV positive diagnosis.
4. Patient has congestive heart failure Class III/IV
5. Patient has had previous exposure to belinostat.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 3 patient groups

Wild Type UGT1A1

Experimental group

Description:

Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV

Treatment:

Drug: Belinostat IV

Heterozygous UGT1A1*28

Experimental group

Description:

Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV

Treatment:

Drug: Belinostat IV

Homozygous UGT1A1*28

Experimental group

Description:

Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV

Treatment:

Drug: Belinostat IV